| 1. |
- Mattsson, Sofia, et al.
(författare)
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Who enrols and graduates from web-based pharmacy education : experiences from Northern Sweden
- 2018
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Ingår i: Currents in pharmacy teaching and learning. - : Elsevier. - 1877-1297. ; 10:8, s. 1004-1012
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: As a response to the shortage of prescriptionists in Northern Sweden, a web-based Bachelor of Science in Pharmacy program was introduced at Umea. University in 2003. This study explored who is likely to enrol and graduate from the web-based bachelor program and whether the program has addressed the shortage of prescriptionists in rural Northern Sweden.Methods: Data from three different sources were included in this study; the initial cohort including students admitted to the program in 2003 (survey), the entire cohort including all people admitted to the program between 2003 and 2014 (university's admissions data) and the alumni cohort including graduates who participated in an alumni survey in 2015.Results: A typical student of the web-based pharmacy program is female, over 30 years of age, married or in a de-facto relationship and has children. Furthermore, the students graduating before 2009 were more likely to live in Northern Sweden compared to those graduating later.Discussion and conclusion: The results indicate that the introduction of a web-based bachelor of pharmacy program at Umea. University was to some extent able to address the shortage of prescriptionists in Northern Sweden. Web-based education may potentially help address the maldistribution of health professionals by providing flexible education opportunities.
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| 2. |
- Ehrenberg, Angelica, et al.
(författare)
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Accounting for strain variations and resistance mutations in the characterization of hepatitis C NS3 protease inhibitors
- 2014
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Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 29:6, s. 868-876
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Tidskriftsartikel (refereegranskat)abstract
- Context: Natural strain variation and rapid resistance development makes development of broad spectrum hepatitis C virus (HCV) drugs very challenging and evaluation of inhibitor selectivity and resistance must account for differences in the catalytic properties of enzyme variants.Objective: To understand how to study selectivity and relationships between efficacy and genotype or resistant mutants for NS3 protease inhibitors.Materials and methods: The catalytic properties of NS3 protease from genotypes 1a, 1b and 3a, and their sensitivities to four structurally and mechanistically different NS3 protease inhibitors have been analysed under different experimental conditions.Results: The optimisation of buffer conditions for each protease variant enabled the comparison of their catalytic properties and sensitivities to the inhibitors. All inhibitors were most effective against genotype 1a protease, with VX-950 having the broadest selectivity.Discussion and conclusion: A new strategy for evaluation of inhibitors relevant for the discovery of broad spectrum HCV drugs was established.
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| 3. |
- Kindstedt, Jonas, et al.
(författare)
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Investigating the effect of clinical pharmacist intervention in transitions of care on drug-related hospital readmissions among the elderly : study protocol for a randomised controlled trial
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Drug-related problems (DRPs) are a major cause of unplanned hospital admissions among elderly people, and transitions of care have been emphasised as a key area for improving patient safety. We have designed a complex clinical pharmacist intervention that targets people >= 75 years of age undergoing transitions of care from hospital to home and primary care. The main objective is to investigate if the intervention can reduce the risk of unplanned drug-related readmission within the first 180 days after the person is discharged from hospital.Methods and analysis: This is a randomised, controlled, superiority trial with two parallel arms. A total of 700 people >= 75 years will be assigned to either intervention or routine care (control). The intervention, which aims to find and manage DRPs, is initiated within a week of the person being discharged from hospital and combines repeated medical chart reviews, phone interviews and in some cases medication reviews. People in both study arms may have been the subject of a medication review during their ward stay. As the primary outcome, we will measure time until unplanned drug-related readmission within 180 days of leaving hospital and use log rank tests and Cox proportional hazard models to analyse differences between the groups. Further investigations of subgroup effects and adjustments of the regression models will be based on heart failure and cognitive impairment as prognostic factors.Ethics and dissemination: The study has been approved by the Regional Ethical Review Board in Umea (registration numbers 2017-69-31M, 2018-83-32M and 2018-254-32M). We intend to publish the results with open access in international peer-reviewed journals and present our findings at international conferences. The trial is expected to result in more than one published article and form part of two PhD theses.
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| 4. |
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| 5. |
- Lampa, Anna, et al.
(författare)
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Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region
- 2014
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 5:3, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1′ 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with Ki-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2–P1′. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1′ 4-(trifluoromethyl)phenyl side chain.
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| 6. |
- Remberger, Mats, et al.
(författare)
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Improved survival after allogeneic hematopoietic stem cell transplantation in recent years : A single-center study
- 2011
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 17:11, s. 1688-1697
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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| 7. |
- Svahn Gustafsson, Sofia
(författare)
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Characterization of HCV Protease Inhibitors : Inhibition and Interaction Studies with Applications for Drug Discovery
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, different approaches based on inhibition and interactions studies, have been used to characterize inhibitors of the non-structural protein 3 (NS3) from the hepatitis C virus (HCV). This involves identification of enzyme inhibitory effects and characterization of interaction mechanisms and kinetics, as well as effects on replication in a cell based system and serum protein binding. All this information contributes to HCV drug discovery.By using an inhibition assay it was possible to evaluate the effects of NS3 protease inhibitors, tested or used in the clinic, on NS3 variants, representing different model systems often used for drug discovery. This study illustrates the importance of accounting for differences in catalytic properties in comparative analyses, for making relevant interpretations of inhibition data. An SPR biosensor-based assay expanded the first study, and provided kinetic and mechanistic information, by direct interaction analyses of the inhibitors. It revealed significant differences between the different genotypes and model systems, and provided data that can be used to better understand the efficacy of inhibitors.Additionally, novel NS3 protease inhibitors were evaluated with respect to their potential to interfere with protease activity, their sensitivity to resistant mutants and effect on HCV replication. The most potent compounds were also characterized by their bioavailability, solubility and metabolic stability. This provides information for design of improved NS3 protease inhibitors, suggesting potential peptidomimetic structures for the backbone as well as for peptide substituents. These modification strategies allowed inhibitors to be truncated and less peptide-like, still with retained inhibitory effect.A new strategy for analysis of serum protein binding, of importance for drug distribution was also developed. By defining and using the concept of binding efficiency, serum protein interactions of moderate affinity, as described by rapid kinetics, were characterized. This strategy is also applicable for analysis of low affinity interactions.Taken together, all these studies provide knowledge and strategies for HCV drug discovery, and by using this information we might take a step closer to the final goal, which is to eradicate HCV.
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| 8. |
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| 9. |
- Svahn, Sofia, et al.
(författare)
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Cardiovascular drug use among people with cognitive impairment living in nursing homes in northern Sweden
- 2020
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Ingår i: European Journal of Clinical Pharmacology. - : Springer. - 0031-6970 .- 1432-1041. ; 76:4, s. 525-537
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this study was to describe changes in the pattern of cardiovascular agents used in elderly people living in nursing homes between 2007 and 2013. Further, the aim was to analyse the use of cardiovascular drugs in relation to cognitive impairment and associated factors within the same population, where prescription of loop diuretics was used as a proxy for heart failure.Methods: Two questionnaire surveys were performed including 2494 people in 2007 and 1654 people in 2013 living in nursing homes in northern Sweden. Data were collected concerning drug use, functioning in activities of daily living (ADL) and cognition, using the Multi-Dimensional Dementia Assessment Scale (MDDAS). The use of different drugs and drug classes among people at four different levels of cognitive function in 2007 and 2013 were compared.Results: The proportion of people prescribed ASA and diuretics was significantly lower at all four levels of cognitive function in 2013 compared to 2007. Among people prescribed loop diuretics, the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARBs) increased from 37.8 to 45.6%, β-blockers from 36.0 to 41.8% and warfarin from 4.4 to 11.4%. The use of warfarin, ACEI/ARBs, β-blockers and mineralocorticoid receptor antagonists (MRAs) were less common among individuals with more severe cognitive impairment.Conclusion: The results indicate that cardiovascular drug treatment has improved between 2007 and 2013, but there is room for further improvement, especially regarding adherence to guidelines for heart failure. Increasing cognitive impairment had an effect on treatment patterns for heart failure and atrial fibrillation.
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